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Fluorescence in Medicine | Malaria | Atabrine | SSRI Research | Goldwater Memorial Hospital | National Heart Institute

Atabrine and the New Pharmacology

The focus of the Goldwater group's antimalarial research was on American Atabrine, a synthetic antimalarial first developed in Germany in the 1930s. Though scientists in the United States had synthesized the drug within a few years, troops did not usually take their medicine. The Atabrine turned them yellow, made them sick, and seemed to take forever to work. What was the problem?

Drs. Brodie and Udenfriend figured out how to measure Atabrine levels in the blood using fluorescence.


Dosage. Army doctors dispensed the Atabrine at the same dose levels they had used for quinine. In the 1940s, however, a new method of dose-setting was coming into vogue, and one of the biggest proponents of what was called the "New Pharmacology" was Dr. James Shannon. At Goldwater, he put Drs. Brodie and Udenfriend on the problem of re-setting the dosage for Atabrine, using this new approach.

First, the scientists had to find a way to measure the concentration of the drug in the blood. Second, they had to figure out what blood concentration would yield the desired result. And third, they had to set a dosage schedule to maintain that desired blood level.

Drs. Brodie and Udenfriend figured out how to measure Atabrine levels in the blood using fluorescence. Since Atabrine fluoresced at a certain wavelength, all they had to do was take a sample of blood plasma from a malarial patient who had taken Atabrine. When seen through a fluorometer, the plasma would "glow" at a level proportional to the amount of Atabrine in the sample.

The scientists found that, at the current dosage, the Atabrine was soaked up in muscle fiber and the liver, causing uncomfortable side effects before it was able to build up in the blood. By changing the dosage-to a first-day big dose to saturate the tissues followed by small daily doses that would then go right to the blood-the Goldwater group was able to save Atabrine, as well as millions of American troops abroad.

Dr. Shannon's so-called "gospel of blood levels" revealed the central importance to pharmacology of being able to measure the concentrations of drugs in the blood. This central issue led the Goldwater team to be interested in a more sensitive instrument than the fluorometer they had used during the war, and therefore led to the development of the SPF.

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